Pharmacokinetic and pharmacodynamic properties of orally administered torsemide in healthy horses.

BackgroundDiuretic treatment is the mainstay for management of congestive heart failure in horses, and its use has been restricted to injectable medications because no currently data supports the use of PO administered loop diuretics. ObjectivesTo determine the pharmacokinetic and pharmacodynamic properties of PO administered torsemide and, determine if PO administered torsemide, could be used as an alternative to injectable diuretics in the horse. AnimalsSix healthy adult mares. MethodsA 2-phase, prospective study, that consisted of pharmacokinetic profiling of a single dose (6 mg/kg PO) and pharmacodynamic effects of long-term torsemide administration (2 mg/kg PO q12h) for 6 days in healthy horses. ResultsPharmacokinetic analysis identified a peak concentration (C-max) of 10.14 mu g/mL (range, 6.79-14.69 mu g/mL) and elimination half-life (T-1/2) 9.2 hours (range, 8.4-10.4 hours). The area under the plasma drug concentration over time curve (AUC) was 80.7 mu g x h/mL (range, 56.5-117.2 mu g x h/mL). A statistically significant increase in urine volume and decrease in urine specific gravity were found from day 0 (baseline) to day 6 (P<.0001). Significant alterations in biochemical variables included hyponatremia, hypokalemia, hypochloremia, and increased serum creatinine concentration. Mean arterial blood pressure significantly decreased on day 6 (57.78.8 mm Hg, P=.001) as compared with baseline (78 +/- 6.1 mm Hg). Serum aldosterone concentrations significantly increased after 6 days of torsemide administration (P=.0006). Conclusions and Clinical ImportancePO administered torsemide (4 mg/kg/day) successfully reached therapeutic concentrations in blood, induced clinically relevant diuresis, and resulted in moderate pre-renal azotemia and electrolyte disturbances.